BRCA1 and BRCA2 are genes that we all have, whose function is to prevent the onset of tumors by repairing damaged DNA molecules. BRCA1 and BRCA2 are thus genes that protect us from the onset of cancers. When one of these genes undergoes a mutation, it loses its protective capacity, making us more susceptible to the appearance of malignant tumors, namely breast cancer, ovarian cancer and prostate cancer.
Cancer is a disease that arises when a cell of an organ or tissue mutates, loses its basic characteristics and starts to multiply in an uncontrolled way, spreading throughout the body. Cancer usually arises when the cell's DNA is injured.
As aggressions to cellular DNA occur all the time, as in cases of exposure to solar radiation, toxins in the air or food, contact with viruses, drug use (licit or illicit), etc., if our body does not have mechanisms of defense, we would all have cancer early. Among the various mechanisms against the onset of tumors are anti-oncogenes, genes responsible for repairing DNA damage. BRCA1 and BRCA2 are two examples of the anti-oncogenes family.
When BRCA1 or BRCA2 anti-oncogenes mutate - and more than 1000 distinct mutations have been identified - they lose the ability to suppress the onset of tumors, leaving the individual more exposed to the development of cancers, especially breast and ovarian cancers. The reason why mutations in BRCA1 and BRCA2 predispose the development of breast and ovary tumors preferentially is not yet clear (as we shall see below, other tumors are also related to the BRCA1 and BRCA2 genes, but in smaller proportions).
The mutant BRCA1 or BRCA2 gene can be passed from one generation to another, which explains the existence of families with a history of breast or ovary cancer in several of its members. There are currently tests to identify the presence of mutations in these two genes, serving to identify early women most susceptible to breast and ovarian cancers.
It should be noted that this mutation is not very common, affecting only about 0.1% of the population.
Women with BRCA1 and BRCA2 mutations have significantly increased risks of breast cancer and ovarian cancer. The risk of breast cancer is 50 to 85% and that of ovarian cancer is between 15 and 45%. The longer the woman lives, the greater her risk of cancer. For example, virtually all women with a mutation of these genes living up to 90 years of age will have had at least one episode of breast cancer in their lifetime. There is also an increased risk of a second diagnosis of breast cancer, that is, the woman with BRCA1 and BRCA2 mutations is at high risk of having a new breast cancer, even if she has managed to cure herself of a previous cancer.
Men bearing the mutant BRCA1 or BRCA2 genes also have an increased risk of breast cancer, but in much smaller proportions than in women, about 10% only. On the other hand, the risk of prostate cancer is up to 5 times higher for BRCA2 mutation carriers, and 2 times higher for BRCA1 gene mutations.
There are other cancers related to mutant BRCA1 or BRCA2 genes, but the frequency is much lower. Examples are cancers of the pancreas, colon, cervix, fallopian tubes, biliary tract and melanoma.
Of all cancers related to BRCA1 or BRCA2 gene mutations, breast cancer is clearly the one with the most intimate relationship. However, since the BRCA1 or BRCA2 mutation is present in only 0.1% of the population, the vast majority of breast cancer cases occur in women without mutations of these genes. We can only identify BRCA1 or BRCA2 gene mutations in about 5 to 10% of all breast cancer cases.
To summarize:
1. the vast majority of women with breast cancer do not have mutations in the BRCA1 or BRCA2 genes.
2. the vast majority of women with mutation of the BRCA1 or BRCA2 genes will have breast cancer at some point in life.
Just as a comparison, on average, 12 out of 100 women in the general population will have breast cancer throughout their lifetime, while in women with mutations in the BRCA1 or BRCA2 genes this rate is 60 for every 100 women.
When screening the mutation in BRCA1 or BRCA2 genes
As only 0.1% of the population has the defective BRCA1 or BRCA2 genes, it is neither practical nor economically feasible to go out searching the gene indiscriminately throughout the world.
The existence of two relatives with breast cancer is not synonymous with having an inherited genetic mutation. Most people or families with breast cancer do not have mutations in the BRCA1 or BRCA2 genes. In order to think about the mutation and, consequently, on the detection of defective genes, some characteristics must be present:
Diagnosis of breast or ovarian cancer in 3 or more family members.
Diagnosis of breast cancer before the age of 50 in at least one family member.
People with 2 distinct episodes of breast cancer (we are not talking about recurrence of the first tumor, but on healing and subsequent onset of a new cancer).
Relatives with breast cancer and ovarian cancer.
Breast cancer in men.
Breast cancer in both breasts.
Patient with breast cancer and several relatives with other cancers, such as pancreas, prostate or colon.
Interpretation of genetic test results for BRCA 1 or BRCA 2 is not always easy to interpret. The results can be:
1. Positive for known mutations of BRCA1 or BRCA2 genes - It means that a mutation that is known to be associated with an increased risk for breast or ovarian cancer has been identified in the patient.
2. Negative Probable - Means that the patient does not have a known mutation of BRCA1 or BRCA2. This result does not exclude the possibility of the patient having a hereditary risk of cancer. Not all mutations are detected in the current tests. In addition, there are many genetic mutations that have not yet been discovered.
3. Real Negative - It means that a mutation of the BRCA1 or BRCA2 known to exist in one of its relatives was discarded in the patient. This result usually means that the risks of breast cancer in the patient are the same as those of other women in the general population.
4. Positive for genetic mutation of unknown meaning - It means that the patient has a genetic mutation, but it is not yet known if this specific mutation increases the risk of breast cancer or ovarian cancer.
Warning: a negative result does not mean that you can not develop a cancer, just as a positive result does not mean that you will develop cancer. In positive test cases, between 50 and 85% of women will develop breast cancer at some point in their lives. In the case of ovarian cancer, this rate is 15 to 45% (higher in BRCA1 than in BRCA2).
What to do when genetic research for BRCA1 or BRCA2 mutations is positive
When the patient receives the news of having a known dangerous mutation of the BRCA1 or BRCA2 genes, some options for the prevention of breast and ovarian cancer should be put on the table.
a) Frequent screening
Women should follow the following malignancy screening routine:
Self-examination of the breast monthly starting at 18 years.
Clinical examination of breasts by an experienced physician two to four times a year, beginning at age 25.
Mammography or MRI of the breast every six months, beginning at age 25.
Screening for ovarian cancer with transvaginal ultrasound and blood levels of CA-125 twice a year, starting at age 35 (or 10 years before the earliest family case).
Men should follow the following malignancy screening routine:
Self-examination of the breast monthly.
Clinical examination of breasts by experienced doctor every six months.
Annual mammography, especially if there is gynecomastia.
Screening appropriate for prostate cancer.
b) Preventive surgery
Bilateral mastectomy (surgical removal of the breasts) and removal of the fallopian tubes and ovaries is a radical option, but with very favorable results in cancer prevention in patients with BRCA1 or BRCA2 gene mutations.
Breast withdrawal reduces the risk of breast cancer by more than 90%. The most effective surgery is total breast withdrawal, but more modern techniques involving nipple and skin preservation appear to have similar results with less cosmetic damage. Most women can do a reconstructive plastic surgery after mastectomy.
In women between the ages of 35 and 40, with offspring already established, removal of the ovaries may also be indicated. This procedure reduces the risk of ovarian cancer by 90% and also contributes to a 60% reduction in breast cancer.
Despite the favorable results, both surgeries have a great emotional impact on patients. Bilateral mastectomy may have unfavorable effects on both self-esteem and the patient's libido. Oophorectomy (removal of the ovaries) leads to early menopause.
c) Drug prevention
A drug called tamoxifen may reduce the risk of breast cancer in women who have BRCA mutations, although the degree of reduction is not yet clear. Hormonal contraceptives (pill, skin patch, vaginal ring or implant) may lower the risk of ovarian cancer.
